Physiology of Blood Circulation
Blood is normally pumped from the heart through a circulatory system comprising a plurality of fluid circuits, each fluid circuit substantially comprising, proximally to distally, arteries of progressively smaller size, capillaries, and veins of progressively larger size. Blood enters capillary beds from precapillary arterioles which normally act as resistance vessels. Having emerged from the heart's left ventricle at (relatively high) arterial pressures, most blood returns to the heart's right atrium via the central veins (the superior and inferior vena cavae) at relatively low pressures. Circulatory system peripheral resistance to blood flow is normally substantially controlled primarily through contraction or relaxation of precapillary arteriolar walls, flow resistance in such arterioles being inversely related to the fourth power of arteriolar radii. Thus, while arterial blood pressures are substantially maintained upstream of capillary beds, capillary blood flow typically occurs at pressures only slightly higher than mean central venous pressure (CVP). And CVP is commonly a small fraction of mean arterial pressure.
Because veins contain blood at relatively lower pressures than arteries of comparable size, venous system vessel walls are generally thinner than arterial walls of similar vessel diameter. Veins are thus more compliant than arteries of comparable diameter, meaning that they are more easily distended by increased intravascular pressure and that they tend to collapse when intravascular pressure falls. These conditions are easily observed as the distended neck veins of a person speaking loudly suddenly flatten while the person pauses to take a breath. Loud speech requires relatively high intrathoracic pressures to expell air forcefully through the vocal cords, but intrathoracic pressure (and thus CVP) drops precipitously as the diaphragm moves downward during inspiration. Veins relatively close to the chest cavity are regularly filled and drained by this intermittent respiratory action. More peripheral veins contain valves which assist in moving blood from dependent areas toward the heart in conjunction with muscle contractions. In all cases, prolonged periods of sustained high venous (and thus high capillary) pressures are avoided to maintain normal capillary function. Note, however, that hemodynamic stability normally requires sufficiently positive CVP to maintain adequate blood flow from the central veins into the heart.
Because of the relatively low blood pressures normally existing in the capillaries and veins, only small pressure gradients normally tend to drive fluid out through capillary and venous walls. Nevertheless, small amounts of fluid can and do leak from the circulating volume (the total volume contained in the heart, arteries, capillaries and veins) into interstitial spaces between the cells of tissues surrounding the blood vessels. A portion of this interstitial fluid can then exchange with intracellular fluids before it is mobilized through lymphatic drainage and eventually returned to the circulating volume through the thoracic duct. Because capillary walls are especially thin (to facilitate gas exchange and the movement of metabolic products and substrates), capillaries tend to be much more compliant than arteries and they leak relatively easily. Thus, relatively small increases in hydrostatic, hydrodynamic and/or osmotic pressure gratients across capillary walls can significantly affect fluid movement through the walls (that is, fluid leaks). In addition to their effect on leaks, pressure changes also cause changes in intravascular volume which for each vessel are described by the vessel compliance (internal volume change per unit internal pressure change).
The human and animal circulatory systems described above are nonlinearly compliant, meaning that vessel compliance is not constant throughout the circulatory system, nor does vessel compliance vary linearly with distance from the heart. Additionally, highly localized nonlinear leaks (usually greatest in the capillaries for given pressures) and nonuniform flow resistance characterize these circulatory systems. This helps explain why maintaining predetermined circulatory system blood flows in the absence of normal heart pumping action (as during total cardiopulmonary bypass) is a complex process which is not achieved without significant time-dependent morbidity with any currently available device.
Venous Pressures During Cardiopulmonary Bypass
During a conventional total cardiopulmonary bypass, pumping and gas exchange functions of a patient are temporarily totally replaced by a pump-oxygenator system. For purposes of this description, a pump-oxygenator system will be considered to comprise one or more pumps and one or more oxygenator/gas exchanger units interconnected as well known to those skilled in the art so as to provide blood withdrawn from a patient with physiologically adequate gas exchange and pressurization before the blood is returned to the patient. Besides gas exchange and pressurization, an additional function performed by extracorporeal apparatus is accumulation of sufficient circulating fluid volume to ensure that, despite fluid losses, sufficient fluid is always available for return (under pressure) to the patient to maintain a desired arterial blood pressure. Thus, the function of a fluid accumulator comprises addition of any fluid volumes necessary to allow performance of the pressurization and gas exchange functions. Note that the three functions described above (gas exchange, pressurization, and accumulation) may take place in any order and in components which are either concentrated or distributed. For purposes of the description herein, pressurization and gas exchange may be accomplished by any apparatus, such as any of the commercially-available pump-oxygenators, known to those of skill in the art to perform those functions. The collective apparatus for pressurization and gas exchange is designated as a pump-oxygenator and represented in flow diagrams herein as a single block, even though its component parts may in fact be distributed.
Whatever the pump-oxygenator configuration, it should be noted that even though the pump-oxygenator pressurizes the blood for return to the patient's arterial circulation, the normally rhythmic rise and fall of intrathoracic pressure associated with spontaneous breathing is eliminated during total cardiopulmonary bypass. Instead, the chest is open and intrathoracic pressure is simply (substantially constant) ambient pressure. This means that the normal rise and fall of CVP during breathing is virtually eliminated, and since the patient is usually paralyzed with a muscle relaxant, circulatory assistance normally provided to venous blood flow by muscle action is also absent. CVP during total bypass is thus usually substantially zero (or even negative) as the patient's venous blood is drained by gravity siphon into a blood accumulator for conveyance through a pump-oxygenator before being returned to the patient's arterial circulation.
Because CVP is substantially zero or negative in conventional total cardiopulmonary bypass (due to withdrawal of a portion of the venous blood volume by siphon into the accumulator), veins throughout the body tend to collapse. Venous flow resistance then rises due to the reduced cross-section of venous flow clannels, but arterial flow resistance tends to fall during cardiopulmonary bypass unless it is altered pharmacologically. Since the artifically raised venous system flow resistance adds algebraically to generally falling arterial flow resistance, the result may be a relatively small change in total peripheral resistance. But instead of being concentrated in the precapillary arterioles, much of the flow resistance moves downstream from the capillary beds into the venous system. Thus, with their drainage artificially impeded by a substantially collapsed venous system, capillary beds during total cardiopulmonary bypass are exposed to a much greater proportion of arterial pressure than they would normally experience. The result is that fluid under the influence of artificially high intracapillary pressures tends to shift from the intravascular space to the interstitial space. Excessive amounts of interstitial fluid, in turn, produce the tissue swelling characteristic of edema.
While maintaining minimum recommended total blood flow rates needed to support gas exchange and other aspects of cellular metabolism, attempts may be made to reduce capillary leak by reducing systemic blood pressures. For example, vasodilators may be administered to the patient to reduce total peripheral resistance in the circulatory system to lower the mean arterial pressure required to maintain adequate blood flow. But the pharmacological effect of vasodilators is primarily to lower arteriolar flow resistance while venous resistance remains artificially high and substantially unaffected. So even if systemic vascular resistance is reduced pharmacologically, mean intracapillary pressure may well remain high enough to significantly increase capillary leaks and their related deleterious effects.
One adverse effect of capillary leaks is that, because high intracapillary pressures tend to drive fluid from the vascular system into the tissues' interstitial space (the "third space"), the patient's edema fluid load increases; it must eventually be mobilized by the patient's lymph system during recovery from the operation.
As intravascular fluid is driven into the tissues by elevated capillary pressures, a second adverse effect becomes apparent. Declining intravascular volume must be replaced by additional fluid, which is usually a combination of crystalloids and colloids. While colloids are desirable to maintain normal colloid osmotic pressure of the intravascular and interstitial fluids, colloids driven into the interstitial spaces are relatively difficult for a patient to mobilize. Crystalloids, on the other hand, are easier to mobilize but tend to move more readily into the intracellular space and to disrupt preferred intravascular and intracellular electrolyte levels (with possible neurological sequelae). Cellular swelling may occur, which adversely affects cellular metabolism and the movement of substrates and products into and out of the cells. Such a reduction in effective contact between cells and circulating blood may effectively create a circulatory shunt which predisposes the patient to cellular hypoxia and lactic acidosis.
A third adverse effect of the capillary leakage described above is the generalized tissue swelling caused primarily by edema fluid. Tissue swelling increases external pressure which tends to collapse the venous drainage channels for capillary beds, raising the channels' flow resistance. In a manner analogous to the air-trapping commonly seen in patients with severe emphysema, fluid tends to become trapped in the capillary beds. When emphysematous patients try harder to exhale, the resulting raised intrathoracic pressure closes the airways ever more tightly and leaves air trapped in the lungs. Similarly, as pump pressure is raised to maintain a predetermined blood flow rate during total cardiopulmonary bypass, capillary leak is further exacerbated, resulting in more edema which eventually calls forth even higher pump pressures.
Thus, edema fluid retention aggravated by excessive capillary blood pressures during total cardiopulmonary bypass can become a significant source of intraoperative and postoperative morbidity and mortality. Costs of supportive care can be significantly increased, and greater susceptibility to other complications (e.g., infections, inflammatory responses, blood clotting abnormalities) reduces the likelihood of a smooth postoperative course.